A subsequent randomized study conducted by ECOG (E1393) compared high-dose paclitaxel (200 mg/m2) as a 24-hour infusion plus cisplatin 75 mg/m2 with G-CSF support, to low dose paclitaxel (135 mg/m2) as a 24-hour infusion, plus cisplatin 75 mg/m2 (Forastiere et al, 2001). Patients with newly diagnosed metastatic or recurrent squamous cell carcinoma of the head and neck, excluding nasopharyngeal primaries were eligible. No prior treatment for recurrent/metastatic disease was allowed, but patients could have received chemotherapy as a part of the initial curative therapy that should have been completed 6 months prior to study. Tow hundred and ten patients were randomized between the 2 arms. No significant difference in outcome was observed. The response rate was 35% vs 36% and the median survival was 7.6 vs 6.8 months, in the high-dose vs low-dose paclitaxel arms respectively. Patients with metastatic disease performed worse in terms of survival. Previously untreated patients achieved a higher response rate of 58% compared to a response rate of 32% observed in patients who have failed prior curative therapies. Substantial toxicities were observed in this trial. Grade 4 neutropenia was seen in 61-71% of patients and febrile neutropenia with hospitalization occurred in 27-39% of patients. The toxic death rate was 10% (12% vs 9%) (Forastiere et al, 2001). It was concluded that the 24-hour paclitaxel infusion was associated with unacceptable toxicity when combined with cisplatin. Instead, a 3-hour paclitaxel infusion combined with cisplatin was advanced to further testing. A more recent randomized trial conducted by ECOG (E1395) compared the combination of paclitaxel 175 mg/m2 as a 3-hour infusion and cisplatin 75 mg/m2 to a standard cisplatin and 5-FU regimen. No statistically significant difference could be demonstrated either in response rates or survival between the two arms (Murphy et al, 2001). This study, however, indicated that paclitaxel, a member of the taxane class of anti-tumor agent, is active in head and neck cancer.